Distal balloon impedance and temperature recording to monitor pulmonary vein ablation and occlusion

ABSTRACT

A cryoablation method, system, and device that allows for real-time and accurate assessment and monitoring of PV occlusion and lesion formation without the need for expensive imaging systems and without patient exposure to radiation. The system includes a cryoballoon catheter with a cryoballoon, a distal electrode, a proximal electrode, and a temperature sensor. Impedance measurements recorded by the electrodes may be used to predict ice formation, quality of pulmonary vein occlusion, and lesion formation.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of patent application Ser. No.15/688107, filed Aug. 28, 2017, entitled DISTAL BALLOON IMPEDANCE ANDTEMPERATURE RECORDING TO MONITOR PULMONARY VEIN ABLATION AND OCCLUSION,and claims priority of patent application Ser. No. 14/560793, filed Dec.4, 2014, entitled DISTAL BALLOON IMPEDANCE AND TEMPERATURE RECORDING TOMONITOR PULMONARY VEIN ABLATION AND OCCLUSION, and is related to andclaims priority to U.S. Provisional Patent Application Ser. No.61912991, filed Dec. 6, 2013, entitled DISTAL BALLOON IMPEDANCE ANDTEMPERATURE RECORDING TO MONITOR PULMONARY VEIN OCCLUSION, the entiretyof which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

n/a

TECHNICAL FIELD

The present invention relates to a cryoablation method, system, anddevice that allows for real-time and accurate assessment and monitoringof ice formation during pulmonary vein ablation using impedancemeasurements recorded by a distal electrode and a proximal electrodecoupled to a cryotreatment device.

BACKGROUND

A cardiac arrhythmia is a condition in which the heart's normal rhythmis disrupted. Certain types of cardiac arrhythmias, includingventricular tachycardia and atrial fibrillation, may be treated byablation (for example, radiofrequency (RF) ablation, cryoablation,ultrasound ablation, laser ablation, microwave ablation, and the like),either endocardially or epicardially.

Procedures such as pulmonary vein isolation (PVI) are commonly used totreat atrial fibrillation. This procedure generally involves the use ofa cryogenic device, such as a catheter, which is positioned at theostium of a pulmonary vein (PV) such that any blood flow exiting the PVinto the left atrium (LA) is completely blocked. Once in position, thecryogenic device may be activated for a sufficient duration to create adesired lesion within myocardial tissue at the PV-LA junction, such as aPV ostium. If a cryoballoon is used as the treatment element of thecryogenic device, the balloon is typically inflated using a fluidcoolant, enabling the balloon to create a circumferential lesion aboutthe ostium and/or antrum of the PV to disrupt aberrant electricalsignals exiting the PV.

The success of this procedure depends largely on the quality of thelesion(s) created during the procedure and whether the cryoballoon hascompletely occluded the PV. For example, a complete circumferentiallesion is produced only when the cryoballoon has completely occluded thePV. Incomplete occlusion allows blood to flow from the PV being treated,past the cryoballoon, and into the left atrium of the heart. This flowof warm blood may prevent the cryoballoon from reaching temperatures lowenough to create permanent lesions in the target tissue. The creation ofreversible lesions may not be sufficient to achieve electrical isolationand, as a result, atrial fibrillation may be likely to reoccur.Additionally, even if the PV is completely occluded, suboptimaloperation of the cryoablation system may result in cryoballoontemperatures that are not low enough, or not applied for a sufficientamount of time, to create permanent lesions in the target tissue.

Current methods of assessing or monitoring PV occlusion includefluoroscopic imaging of radiopaque contrast medium injected from thedevice into the PV. If the device, such as a cryoballoon catheter, hasnot completely occluded the PV ostium, some of the contrast medium mayflow from the PV into the left atrium. In that case, the device may berepositioned and more contrast medium injected into the PV. This methodnot only necessitates the use of an auxiliary imaging system, but italso exposes the patient to potentially large doses of contrast mediumand radiation. Alternatively, pressure measurement distal to theocclusion site can be used to assess occlusion prior to initiating thecoolant injection. Other methods may involve the use of temperaturesensors to determine the temperature within the cryoballoon and tocorrelate the measured temperature to a predicted thickness of icecreated in tissue that is in contact with the cryoballoon. However, itmay be difficult to accurately determine ice thickness based on balloontemperature alone and this latter method can only be used during coolantinjection.

During cryoablation, ice forms between the cryoballoon and adjacenttissue, and this contributes to lesion formation. Additionally, iceformation between a cryotreatment element and adjacent tissue may be anindicator of PV occlusion. The greater the volume of warm blood thatpasses over the cryoballoon, the slower ice formation will occur, andthe thinner the layer of the formed ice may be. However, direct meansfor measuring PV occlusion, ice formation, and/or ice thickness (andtherefore PV ablation) are not available.

It is therefore desirable to provide a cryoablation method, system, anddevice that allows for real-time and accurate assessment and monitoringof ice formation during PV ablation without the need for expensiveimaging systems and without patient exposure to radiation. It is furtherdesirable to provide a means for using ice formation as an indicator ofthe presence and/or quality of PV ablation.

SUMMARY

The present invention advantageously provides a cryoablation method,system, and device that allows for real-time and accurate assessment andmonitoring of PV ablation and occlusion without the need for expensiveimaging systems and without patient exposure to radiation. The presentinvention further provides a means for using ice formation as anindicator of the presence and/or quality of PV ablation. The presentinvention also provides a cryoablation system and method that mayaccurately monitor lesion formation in real time, based on changes inthe impedance measurements. A method of assessing lesion quality inpulmonary vein ostium tissue may include recording a first set ofimpedance measurements from an electrode on a balloon catheter having atreatment element at a distal portion, recording a second set ofimpedance measurements from the electrode, determining a first impedanceslope using the first set of impedance measurements and determining asecond impedance slope using the second set of impedance measurements,comparing the first slope to a first reference slope and the secondslope to a second reference slope, and determining whether the ballooncatheter is creating a permanent lesion in tissue surrounding thepulmonary vein (for example, a pulmonary vein antrum and/or ostium)based on the comparison of the first slope to the first reference slopeand the second slope the second reference slope. Depending on thedetermination, the treatment element of the balloon catheter may berepositioned if lesion quality is poor (that is, if a permanent lesionis not being created in the tissue surrounding the pulmonary vein, suchas pulmonary vein ostium tissue). The method may also include recordinga set of temperature measurements and comparing the set of temperaturemeasurements to the first slope and second slope of impedancemeasurements and comparing the set of temperature measurements to areference temperature. The set of temperature measurements may berecorded from a thermocouple on the balloon catheter or the firstelectrode. The electrode may be located distal to the treatment element,such as at a location immediately distal to the treatment element. Theelectrode may be a first electrode, and the method may also includerecording a first set of impedance measurements from a second electrodeon the balloon catheter, recording a second set of impedancemeasurements from the second electrode, determining a third impedanceslope using the first set of impedance measurements from the secondelectrode and determining a fourth impedance slope using the second setof impedance measurements from the second electrode, comparing the thirdslope and the fourth slope, comparing the first slope and the thirdslope, comparing the second slope and the fourth slope, and determining,based on the comparison between the first, second, third, and fourthslopes, whether the balloon catheter is creating a permanent lesion inthe tissue pulmonary vein ostium tissue. Based on the determination, thetreatment element may be repositioned until it is determined that thetreatment element is creating a permanent lesion. The first electrodemay be located distal to the treatment element, such as distal to andadjacent to the treatment element, and the second electrode may belocated either distal to the first electrode or proximal to thetreatment element. The thermocouple may be proximate the firstelectrode. The first slope and the second slope may at least partiallydefine an impedance curve, and the impedance curve may representimpedance measured by at least the first electrode when the pulmonaryvein is completely occluded. Further, the comparison between the firstand second slopes may indicate a thickness of ice formed when thetreatment element is activated. Further, determining whether the ballooncatheter is creating a permanent lesion in the pulmonary vein tissue mayinclude correlating the ice thickness to the creation of a permanentlesion by the balloon catheter. For example, a determination ofpermanent lesion formation may be made when the ice thickness is atleast 3 mm or an impedance measured by the electrode is at least 2000Ω.As a further example, a determination of permanent lesion formation maybe made when an impedance measured by the electrode is at least 2000Ωwithin 120±30 seconds.

A method of assessing pulmonary vein ostium lesion quality may includepositioning a balloon catheter proximate a pulmonary vein ostium, theballoon catheter including a longitudinal axis and a balloon; reducingthe temperature of the balloon to a temperature sufficient to ablate anostium of the pulmonary vein; recording a first set of impedancemeasurements from each of a plurality of electrodes radially disposedabout the longitudinal axis immediately distal to the balloon; recordinga second set of impedance measurements from each of the plurality ofelectrodes; determining a first impedance slope using the first set ofimpedance measurements from each of the plurality of electrodes anddetermining a second impedance slope using the second set of impedancemeasurements from each of the plurality of electrodes; comparing thefirst impedance slope and the second impedance slope for each of theplurality of electrodes to generate an impedance curve for each of theplurality of electrodes; comparing the impedance curves of the pluralityof electrodes to each other; determining, based on the comparisonbetween the impedance curves, at least one of: whether the ballooncatheter is creating a permanent lesion in the pulmonary vein ostium;whether the balloon catheter is not occluding the pulmonary vein;whether the balloon catheter is partially occluding the pulmonary vein;and whether the balloon catheter is completely occluding the pulmonaryvein; determining, when the comparison indicates that the ballooncatheter is partially occluding the pulmonary vein, a radial position ofan area of the treatment element that is not in contact with tissue; andrepositioning the treatment element until a determination of at leastone of complete occlusion and the creation of a permanent lesion ismade.

A method of determining cryoablation lesion quality may include:positioning a cryoballoon coupled to an ablation catheter in contactwith a pulmonary vein ostium, the ablation catheter further including: afirst electrode immediately distal to the cryoballoon; a secondelectrode distal to the first electrode; and at least one thermocoupleproximate the first electrode, the first and second electrodes beingwithin the pulmonary vein; initiating a flow of coolant within thecryoballoon to cool the cryoballoon to a temperature sufficient toablate the pulmonary vein ostium; continuously recording impedancemeasurements from the first electrode; continuously recording impedancemeasurements from the second electrode; continuously recordingtemperature measurements from the thermocouple; and determining that acircumferential ablation lesion will be formed around the pulmonary veinostium when the first electrode measures an impedance of at least 2000Ωand the thermocouple measures a temperature of −37.8±3.3° C. within120±30 sec from the onset of the flow of coolant within the cryoballoon.

A system for cryoablating tissue may include: a cryoablation device, thedevice including: a balloon coupled to a distal portion of the device; afirst electrode immediately distal to the balloon; a second electrode adistance from the first electrode; and at least one thermocoupleproximate the first electrode; a source of coolant in fluidcommunication with the balloon; and a console including a processor, theprocessor programmed to: receive impedance measurements recorded by thefirst and second electrodes; receive temperature measurements recordedby the thermocouple; and determine whether the balloon is creating apermanent lesion in a pulmonary vein ostium, the determination based onat least one of the impedance measurements from the first electrode,impedance measurements from the second electrode, and temperaturemeasurements from the at least one thermocouple. The processor may befurther programmed to calculate a thickness of ice formed between theballoon and the pulmonary vein ostium and determine that the balloonwill create a substantially circumferential lesion about the pulmonaryvein ostium when the processor determines that the ice thickness is atleast 3 mm.

The second electrode may be proximal to the balloon, and the processormay be further programmed to compare impedance measured by the firstelectrode to impedance measured by the second electrode and determinewhether the balloon is completely occluding the pulmonary vein based onthe comparison between the impedance measured by the first electrode andthe impedance measured by the second electrode.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and theattendant advantages and features thereof, will be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1A shows an exemplary cryotreatment system including a firstembodiment of a cryoballoon catheter;

FIG. 1B shows a close-up, cross-sectional view of a distal portion of acryoballoon catheter, with the delivery of coolant being directed towardthe distal portion of the cryoballoon;

FIG. 2 shows a close-up view of the distal portion of the firstembodiment of a cryoballoon catheter;

FIG. 3 shows a close-up view of the distal portion of a secondembodiment of a cryoballoon catheter;

FIG. 4 shows a close-up view of the distal portion of a third embodimentof a cryoballoon catheter;

FIG. 5 shows a cryoballoon catheter within a heart;

FIG. 6A show a graph illustrating change in impedance over time during acryotreatment procedure with the pulmonary vein is occluded;

FIG. 6B shows a graph illustrating a change in temperature over timeduring a cryotreatment procedure with the pulmonary vein occluded;

FIG. 6C shows a graph illustrating change in impedance over time duringa cryotreatment procedure with the pulmonary vein not occluded;

FIG. 6D shows a graph illustrating a change in temperature over timeduring a cryotreatment procedure with the pulmonary vein not occluded;

FIG. 7 shows a graph illustrating change in impedance over time during acryotreatment procedure with the pulmonary vein completely occluded,partially occluded, and not occluded;

FIGS. 8A and 8B show graphs representing temperature and impedancemeasurements plotted against ice thickness; and

FIG. 9 shows a schematic representation of an experimental setup forcorrelating ice formation with impedance.

DETAILED DESCRIPTION

Referring now to FIG. 1A, an exemplary cryotreatment system is shown.The system 10 may generally include a treatment device, such as acryotreatment catheter 12, for thermally treating an area of tissue anda console 14 that houses various system 10 controls. The system 10 maybe adapted for a cryotreatment procedure, such as cryoablation. Thesystem 10 may additionally be adapted for radiofrequency (RF) ablationand/or phased RF ablation, ultrasound ablation, laser ablation,microwave ablation, hot balloon ablation, or other ablation methods orcombinations thereof. The system 10 may also include a mapping catheter16 (shown in FIG. 5) for sensing and recording electrical signals fromtissue (for example, cardiac tissue).

The cryotreatment catheter 12 may generally include a handle 18, anelongate body 20 having a distal portion 22 and a proximal portion 24,one or more treatment elements 26, a shaft 28, a distal electrode 30, aproximal electrode 31, and a longitudinal axis 32. Each of the distalelectrode 30 and proximal electrode 31 may be configured to measure bothimpedance and temperature. Alternatively, each electrode 30, 31 maymeasure impedance only. The device 12 may further include a referenceelectrode 33 and one or more temperature sensors 34, such asthermocouples for measuring temperature if the electrodes 30, 31 are notconfigured to measure temperature (as shown in FIG. 3). The treatmentelement 26 may be a cryoballoon, as shown in FIGS. 1A-4. The cryoballoon26 may be coupled to the distal portion 22 of the elongate body 20 ofthe cryotreatment catheter 12. For example, the cryoballoon 26 maydefine a proximal portion or neck 36 that is affixed to or coupled tothe distal portion 22 of the elongate body 20, and may further define adistal portion or neck 38 that is affixed to or coupled to the shaft 28(such as the distal portion 40 of the shaft 28). However, it will beunderstood that the cryoballoon 26 may be coupled, affixed, disposed on,integrated with, or otherwise attached to the elongate body 20 and/orthe shaft 28. Additionally, multiple cryoballoons may be used, such aswhen the cryoballoon 26 is disposed within or without a secondcryoballoon (not shown). The shaft 28 may lie along the longitudinalaxis 32 and be longitudinally movable within the elongate body 20. Inthis manner, longitudinal movement of the shaft 28 will affect the shapeof the cryoballoon 26. The proximal portion of the shaft 28 may be inmechanical communication with one or more steering mechanisms 42 in thehandle 18 of the cryotreatment catheter 12, such that the shaft 28 maybe longitudinally extended or retracted using one or more steeringmechanisms 42, such as knobs, levers, wheels, pull cords, and the like.

In addition to the shaft 28, the cryotreatment catheter 12 may includeone or more lumens, such as a fluid injection lumen 43 and a fluidrecovery lumen, for circulating coolant through from a fluid reservoir(which may be part of, disposed within, and/or in communication with theconsole 14) through the elongate body and to the cryoballoon 26, and forrecovering expended coolant from the cryoballoon 26 and collecting theexpended coolant within a fluid reservoir or venting to the atmosphere.Further, the cryotreatment catheter 12 may include a fluid deliveryelement 44 that is in fluid communication with the fluid injection lumen43. As a non-limiting example, the fluid delivery element 44 may bewound about at least a portion of the shaft 28 within the cryoballoon26, as shown in FIG. 1B. The fluid delivery element 44 may be configuredto direct a spray of coolant toward the distal portion of thecryoballoon 26. For example, the fluid delivery element 44 may include aplurality of outlet ports 45 that are configured to deliver fluid at anangle a from the longitudinal axis 32 of the device, such as at an anglea of between approximately 30° and approximately 45° (±5°). However, itwill be understood that the fluid delivery element 44 may have anyconfiguration that is suitable for directing fluid toward the distalportion of the cryoballoon 26. If the cryotreatment catheter 12 includesthermoelectric cooling elements or electrodes capable of transmittingradiofrequency (RF), ultrasound, microwave, electroporation energy, orthe like, the elongate body 18 may include a lumen in electricalcommunication with an energy generator (which may be part of, disposedwithin, and/or in communication with the console 14).

The mapping catheter 16 may be passable (longitudinally movable) throughthe shaft 28. The mapping catheter 16 may include one or more pairs ofmapping elements 46, such as electrodes capable of sensing and recordingelectrograms from cardiac tissue. The one or more pairs of mappingelements 46 may be composed of metal or other electrically conductivematerial and may be affixed on an outer surface of the mapping catheter16, integrated and flush with the body of the mapping catheter 16 (suchthat the mapping catheter has a smooth outer surface), may be areas ofexposed electrically conductive material (for example, where an outerinsulative layer has been removed), or may be otherwise affixed, coupledto, or integrated with the mapping catheter 16. The mapping catheter 16may be in deformable and/or steerable using one or more steeringmechanisms 42 into a variety of configurations. For example, the distalof the mapping catheter 16 may be deformable into a lasso-typeconfiguration, such that the loop portion 50 and mapping elements 46 maybe in contact with at least a portion of an inner circumference of a PV.

The console 14 may be in electrical and fluid communication with thecryotreatment catheter 12 and the mapping catheter 16, and may includeone or more fluid (for example, cryotreatment coolant) reservoirs,coolant recovery reservoirs, energy generators 51, and computers 52 withdisplays 54, and may further include various other displays, screens,user input controls, keyboards, buttons, valves, conduits, connectors,power sources, processors, and computers for adjusting and monitoringsystem 10 parameters. As used herein, the term “computer” may refer toany programmable data-processing unit, including a smart phone,dedicated internal circuitry, user control device, or the like. Thecomputer 52 may include one or more processors 56 that are in electricalcommunication with the one or more pairs of mapping elements 46, the oneor more electrodes 30, 31, the one or more treatment elements 26, andone or more valves and programmable to execute an algorithm for locatingone or more optimal treatment areas, for controlling the temperature ofthe one or more treatment elements 26, for generating one or moredisplays or alerts to notify the user of various system criteria ordeterminations, and/or for predicting temperature within target tissuebased at least in part on signals from one or more of the temperaturesensors 34. As a non-limiting embodiment, the proximal portion of themapping catheter 16 may include an electrical connection that ismateable to at least a portion of the console (for example, with theelectrophysiology recording equipment) and in electrical communicationwith the one or more processors 56. Additionally, the electrodes 30, 31may be in electrical communication with an energy generator 51 for theapplication of energy to the electrodes 30, 31 for sensing impedanceand, optionally, for mapping cardiac electrograms from adjacent tissue.

The console 14 may also include one or more valves that are inelectrical and/or mechanical communication with, and controllable by,the console 14. For example, the computer 52 and/or one or moreprocessors 56 may be programmable to control various system components,such as the one or more valves, to operate according to a duty cyclethat includes opening and closing the one or more valves to regulate theflow of coolant through the system 10 and the catheter 12, and tothereby regulate the temperature of the treatment element 26 (forexample, the cryoballoon 26). The duty cycle may be programmable by theuser and/or may be automatically set by the console 14 according to apredicted tissue temperature based at least in part on signals from oneor more of the electrodes 30, 31, and/or temperature sensors 34.

Referring now to FIG. 2, a close-up view of the distal portion of afirst embodiment of the cryoballoon catheter is shown. As shown anddescribed in FIGS. lA and 1B, the cryotreatment device 12 may includeone or more distal electrodes 30 and one or more proximal electrodes 31.The device 12 may further include a reference electrode 33 and one ormore thermocouples 34 if the electrodes 30, 31 are not configured tomeasure temperature. The electrodes 30, 31, 33 may be composed of anelectrically conductive material suitable for sensing impedance and,optionally, temperature. In the embodiment shown in FIGS. 1A-2, bothelectrodes 30, 31 and thermocouple 34 may be located distal to thecryoballoon 26. Electrodes 30, 31, 33 and thermocouple 34 may be coupledto, affixed to, disposed about, integrated with, or otherwise located ona distal portion of the device 12. The proximal electrode 31 may belocated immediately distal to the cryoballoon 26, such as on the shaftdistal portion 40. For example, the proximal electrode 31 may beadjacent to or abut the distal end of the cryoballoon 26. The distalelectrode 30 may be located a distance from the proximal electrode 31.For example, the distal electrode 30 may be located approximately 2 mmdistal to the proximal electrode 31. The cryotreatment device 12 mayfurther include a thermocouple 34 for measuring temperature. Thethermocouple 34 may be located a distance from the distal electrode 30.For example, the thermocouple 34 may be located approximately 2 mmdistal to the distal electrode 30. Temperature monitoring may provide anadditional and/or redundant means of assessing the quality of the freezeand propagation of the freeze in the tissue. As a non-limiting example,the balloon may have a diameter of approximately 23 mm to approximately28 mm.

Alternatively, as shown in FIG. 3, the distal electrode 30 may belocated immediately adjacent to the cryoballoon 26 and the proximalelectrode 31 may be located proximal to the cryoballoon 26, such as onthe elongate body distal portion 22. For example, the distal electrode30 may be adjacent to or may abut the distal end of the cryoballoon 26.However, the proximal electrode 31 may alternatively be located on asheath or a separate catheter. The proximal electrode 31 may be somewhatlarger than the distal electrode 30, and may serve as the indifferent ina bipolar impedance circuit or reference electrode. The larger size ofthe proximal electrode 31 may minimize the impedance drop on theelectrode 31, making the circuit more sensitive to change on the distalelectrode 30. Since the electrode 31 is proximal to the cryoballoon 26,it may be more sensitive to occlusion changes because the directelectrical path through the blood pool is eliminated. The placement ofelectrodes 30, 31 shown in FIG. 3 additionally may allow thecryotreatment device 12 to be integrated with conventionalelectropotential navigation systems such as NavX, CARTO 3, and LocaLisa.Although not shown in FIGS. 2 and 4, the device 12 may also include areference electrode 33 as shown and described in FIGS. 1A-2 and 5.

Referring now to FIG. 4, a close-up view of the distal portion of asecond embodiment of a cryoballoon catheter is shown. The embodimentshown in FIG. 4 is generally similar to those shown in FIGS. 1A-3. Likethe embodiment shown in FIGS. 1A-3, the cryotreatment device 12 shown inFIG. 4 may include a proximal electrode 31 that is located proximal tothe cryoballoon 26. Instead of a distal electrode 30, however, thedevice 12 may include a plurality of discrete electrodes 58A, 58B, 58C,. . . radially disposed about the shaft distal portion 40 immediatelydistal to the cryoballoon 26. For example, each electrode 58 may beradially spaced about the longitudinal axis of the device and may beadjacent to or may abut the cryoballoon 26. Each electrode 58 may bemonitored individually, allowing the user and/or console 14 to evaluatethe symmetry of the impedance rise and therefore the ice formation. Forexample, a small leak of blood form the PV past one side of thecryoballoon 26 may result in a slower impedance rise on the electrode 58closest to the leak. In addition to sensing impedance, the electrodes30, 31, 58 of any embodiment may also be configured for mapping cardiactissue (for example, recording cardiac electrograms) from adjacenttissue. In a non-limiting embodiment, the discrete electrodes 58 may beradially arranged in a distal housing coupled to the shaft distalportion 40, and each electrode 58 may protrude from the housing (forexample, may be dome shaped) to facilitate local tissue depolarizationfor tissue mapping. Additionally or alternatively, the electrodes 58 maybe used for electrical impedance tomography imaging to “see” the iceformation.

Regardless of the configuration of the electrodes (that is, whether theelectrodes are as shown and described in FIGS. 1A-4), the fluid deliveryelement 44 may still direct fluid toward the distal end of thecryoballoon 26. In this way, ice may form more quickly on the one ormore electrodes located distal to the cryoballoon 26.

Referring now to FIG. 5, a cryotreatment catheter is shown positionedproximate a pulmonary vein ostium for a pulmonary vein ablationprocedure (which may also be referred to as a pulmonary vein isolation(PVI) procedure). As used herein, the term “PV tissue” or “pulmonaryvein tissue” may include tissue of the PV ostium, the PV antrum, LA walltissue, and/or tissue at the junction between the LA and PV, and is notlimited to tissue within the PV. In fact, ablation of tissue within thePV may be undesirable. The inflated cryoballoon 26 may be positioned atthe pulmonary vein (PV) ostium to occlude the PV, or block the flow ofblood from the PV into the left atrium (LA) of the heart. Occlusion ofthe PV not only serves to position the cryoballoon 26 to create acircumferential lesion around the PV ostium, but also prevents warmblood from flowing over the portions of the cryoballoon 26 that are incontact with the target tissue, thereby enhancing the ability of thecryoballoon 26 to reach sufficiently cold temperatures for creatingpermanent, and circumferential, cryoablation lesions on or in the targettissue. If the PV is not completely occluded, blood flow past thecryoballoon 26 may have the effect of raising the temperature of thecryoballoon 26, possibly resulting in the formation of reversiblelesions on or in the target tissue. The blocked blood within the PV maybe referred to as “stagnant” blood, whereas the blood within the LA maybe referred to as “flowing” blood, as blood may still enter the LA fromthe other three PVs that are not being occluded by the catheter 12.

As shown in FIG. 5, the cryoballoon 26 may be positioned at the PVostium such that the shaft distal portion 40 is disposed within the PV,within the stagnant blood. Continuous impedance and temperaturemeasurements may be taken during device placement and, subsequently,cryoablation. Impedance may increase as at least part of the cryoballoon26 is inserted into the PV, which may indicate either full or partialocclusion. The amplitude of the impedance increase may be used todetermine whether the occlusion is full or partial and, therefore, maybe used to determine whether permanent lesions are being formed. Forexample, a greater amplitude may indicate full occlusion, whereas alesser amplitude may indicate partial occlusion. Full occlusion may beindicative of permanent lesion formation as a result of the ablationprocedure. If impedance and/or temperature measurements indicate thatthe PV is not permanently ablated and/or less than fully occluded, thedevice may be repositioned until complete PV occlusion is indicated byevaluation of the impedance and/or temperature measurements. Forexample, the one or more processors 56 of the console computer 52 may beprogrammed to receive and process data from the one or more electrodesand/or thermocouples, and to generate an alert to the user indicatingthat the device should be repositioned to achieve complete PV occlusionor that the device is already optimally positioned.

Referring now to FIGS. 6A-7, graphs illustrating the change in impedanceand temperature over time are shown. The graphs show in FIGS. 6A-6D shownon-limiting, experimental data. Each line in the charts (lines 1-4 inFIGS. 6A and 6B, and lines 1-5 in FIGS. 6C and 6D) is a unique set oftest data. Impedance changes during cryoablation may be correlated tothe ice thickness at the distal portion of the cryoballoon 26 (thethickness of the ice covering the distal electrode 30), which isdirectly related to the ice formation occurring at the perimeter of thecryoballoon 26. The processor 56 of the console computer 52 may beprogrammed or programmable to execute an algorithm for this correlationand display the results to the user. For example, based on impedancemeasurements, the computer 52 may display to the user text, graphicalicons, or other indicia indicating complete or partial PV occlusion orlack of PV occlusion, which may indicate lesion quality. If theimpedance immediately increases (as shown in FIG. 6A), this may indicatethat the PV ostium is occluded and the freeze will be of high quality(that is, the PV ostium lesion will be circumferential and permanent).The duration of the cryoablation may be defined by the thickness of thesurrounding myocardium and the impedance rise required to create iceacross the entire thickness of the myocardium. As shown in FIG. 6A,complete occlusion may cause the impedance to rise rapidly withtemperature crossing the 0° C. mark beginning at approximately 60seconds into the cryoablation procedure. Impedance may continue to riseto 2000Ω (ohms) or above and temperature may decrease to approximately−37.8±3.3° C. at 120±30 seconds. If the impedance rise is delayed, onthe other hand, this may indicate that an ice bridge was required toclose a gap that had been allowing blood to flow past the distal portionof the cryoballoon 26. The impedance rise and time may then be adjustedto accommodate for this delay. Finally, if the impedance does not riseor is substantially delayed (as shown in FIG. 6C), this may indicatethat the quality of the freeze is low because blood is flowing past thetip of the balloon, preventing the creation of a permanent,circumferential lesion. In this situation, the user may choose to stopthe cryoablation and/or reposition the cryoballoon 26. As shown in FIG.6C, impedance may not rise above 500Ω, with the temperature reachingonly approximately −9.2±12.1° C. Ice thickness may grow significantlystarting at approximately 60 seconds into the cryoablation beforestabilizing at a thickness of approximately 3±0.5 mm. As shown in FIGS.6B and 6D, temperature trends may follow impedance trends, with a sharpdecrease and lower possible temperature being reached with fullocclusion (as shown in FIG. 6B) and a less defined decrease and warmerpossible temperature being reached with no occlusion (as shown in FIG.6D).

Impedance and temperature measurements by one or more electrodesproximate the balloon, such as the distal electrode 30 of the deviceshown in FIG. 3 or the proximal electrode shown in FIG. 2, may becorrelated to ice thickness, which, in turn, may be correlated toocclusion and lesion quality. Further, impedance may continue to riseeven after ice formation. Monitoring this impedance during acryotreatment procedure (that is, during the circulation of cryogenicfluid within the cryoballoon 26) may help an operator to determine whento stop the cryotreatment procedure. For example, the measured impedancemay rise to approximately 2000 S2 within approximately two or threeminutes. An impedance value above this level, associated with a longertreatment time, may indicate that the cryotreatment procedure may becausing collateral damage to non-target tissue.

FIG. 7 shows change in impedance with full occlusion, partial occlusion,and no occlusion. The distal 30 and proximal 31 electrodes referred toin discussing FIG. 7 may be configured as shown, for example, in FIG. 2,wherein the proximal electrode 31 is distal to the balloon 26, betweenthe distal electrode and the balloon 26. However, it will be understoodthat similar measurements may be recorded by the distal 30 and proximal31 electrodes configured as shown in FIGS. 2 and 4. Thus, in theexemplary curves shown in FIG. 7, the proximal electrode 30 may belocated closer to the balloon than the distal electrode 30 and willtherefore be more thermally affected by the balloon.

The shape of the impedance curve may provide useful informationregarding the quality of the freeze (for example, the curve timing,initial and final slope, and peak). When the PV is fully occluded, icewill form rapidly and impedance will rise rapidly, reachingapproximately 2000Ω within approximately two or three minutes (asmeasured by the proximal distal electrode 30). The impedance rise may benoted by the distal electrode 30 within approximately 90 seconds. Asshown in FIG. 7, the slope of impedance measured by both the distalelectrode 30 and the proximal electrode 31 is positive. The slope ofimpedance measured by the proximal electrode 31 may include a firstphase (referred to as V_(FOslope-1)) having a first slope measuredbetween approximately 0 seconds and approximately 60 seconds (±10seconds) and a second phase as the ice ball expands (referred to asV_(FOslope-2)) having a second slope measured between approximately 60seconds and approximately 90 seconds (±10 seconds). In the non-limitingtest 4 data shown in FIG. 6A, the slope of the first phase first phase(between approximately 0 seconds and approximately 60 seconds) is lessthan the slope of the second phase (between approximately 60 seconds andapproximately 90 seconds. In the first phase, the rate of impedanceincrease is approximately 200Ω/minute (±100Ω), which may be used as afirst reference slope, and this rate then increases to approximately2000Ω/minute (±100Ω), which may be used as a second reference slope, inthe second phase. This is indicative good ice ball formation. Further,impedance measured after the second phase, for example, betweenapproximately 90 seconds and approximately 180 seconds (±10 seconds) mayplateau, as shown in test 4 data in FIG. 6A. This may indicate that nofurther ice ball formation will take place. Measured slopes in the firstand second phases may be compared to the first and second referenceslopes that are indicative of good occlusion and, therefore, good lesionquality. As discussed below, the rate of impedance increase in both thefirst and second phases when there is poor occlusion may beapproximately 200Ω/minute, and the rate of impedance increase withpartial occlusion may be approximately 200Ω/minute in the first phaseand approximately 1000Ω/minute in the second phase. However, it will beunderstood that these rates are exemplary, and may vary by patient.

Upon termination of cryoablation, the impedance sensed by the distalelectrode 30 may initially decrease in the same way as the impedancesensed by the proximal electrode 31. The distal electrode 30 may recoverfaster than the proximal electrode 31 since the distal electrode 30 isless thermally affected by the balloon.

When the PV is partially occluded, the impedance increase, slopeV_(POslope-1), may be similar to that (V_(FOslope-1)) when the PV iscompletely occluded. As a non-limiting example, the rate of impedanceincrease may be approximately 200Ω/minute (±100Ω). However, the slope ofthe second phase (V_(POslope-2)) measured by the proximal electrode 31may be slower that when there is full occlusion (V_(FOslope-2)),suggesting a slower ice expansion when the PV is partially occluded. Asa non-limiting example, the rate of impedance increase in the secondphase with full occlusion may be approximately 2000Ω/minute (±100Ω),whereas the rate of impedance increase in the second phase with onlypartial occlusion may be only approximately 1000Ω/minute (±100Ω). Bloodmay flow past the balloon with partial occlusion, and therefore the icemay reach the distal electrode 30 more slowly and the rate of impedanceincrease sensed by the distal electrode 30 may also be slower because itmay take time for the ice to reach the distal electrode 30. However, therate of ice expansion from the balloon to the proximal electrode 31 tothe distal electrode 30 when the PV is completely occluded may be fasterthan when the PV is partially occluded. When the PV is not occluded, icemay not reach the distal electrode 30 at all. The distance the icetravels from the balloon (for example, as measured by the electrodes 30,31) may indicate ice thickness. If ice thickness reaches approximately 3mm, complete occlusion and, therefore, good lesion quality, may beindicated. Likewise, an increase in impedance to at least 2000 ohms (Ω)may also indicate complete occlusion and, as a result, good lesionquality. Impedance may be continuously during the cryotreatmentprocedure, even after the distal electrodes become covered in ice.

When the PV is not occluded, the initial impedance rise, V_(NOslope-1),may be the same as with complete or partial occlusion (V_(FOslope-1) andV_(POslope-1), respectively); however, the first phase, V_(NOslope-1),may be followed by a slow second phase, V_(NOslope-2) (which may be evenslower than the second phase, V_(POslope-2), than when the PV ispartially occluded) and the impedance sensed by the distal electrode 30may rise very slowly. Non-limiting examples of the similarity betweenthe first phase, V_(NOslope-1), and the second phase, V_(POslope-2),with no occlusion is shown in FIG. 6C. In all five tests, the slope ofthe second phase is very similar to the slope of the first phase. As anon-limiting example, the rate of increase in both the first and secondphases may be approximately 200Ω/minute (±100Ω). The recovery phase maybe similar for both electrodes 30, 31. When the ice expansion is veryslow and limited, the total impedance rise may be lower (as shown by thesmallest curve in FIG. 7) and the rate of ice expansion in the secondphase may be limited. For example, if the second phase is flat or nearlyflat, this may indicate that no further ice expansion will take place.

FIGS. 8A and 8B show graphs representing temperature and impedancemeasurements plotted against ice thickness. As is shown, ice thicknessincreases as temperature decreases, but at a certain temperature, icethickness plateaus. As is further shown, as ice thickness increases,impedance increases.

It may be concluded that ice thickness correlates with impedance if fullocclusion is present. Further, PV isolation (that is, the formation of apermanent, circumferential lesion) may be achieved with approximately 3mm of ice formation and an impedance rise of more than 2000 ohms. Icethickness may be determined and/or confirmed using techniques such asultrasound. An experimental setup such as that shown in FIG. 9 (stylizedrepresentation shown) may be used to correlate ice formation withimpedance. For example, a cryotreatment device 12 including a proximal31 and distal 30 electrodes may be inserted into a tissue sleeve, suchas the superior vena cava of the heart. Saline having a temperature ofapproximately 37° C. may be circulated through the tissue sleeve towardthe cryoballoon 26. As the cryoablation procedure is conducted,impedance and temperature may be continuously monitored. Further, anultrasound probe may be used to evaluate the thickness of ice forming inthe tissue sleeve. The ice thickness may then be correlated to theimpedance measurements.

Impedance changes may also be combined with measurements such as time toresponse, time to electrogram disappearance (as recorded by the mappingcatheter 16 and/or the distal 30 and proximal 31 electrodes), and/orrate of change in temperature in order to further improve the system'sability to evaluate PV occlusion and, therefore, lesion quality.Additionally, impedance changes may be combined with pressure changes tofurther improve the system's ability to evaluate PV ablation andocclusion. In such a case, the cryotreatment device 12 may furtherinclude one or more pressure sensors at various locations on the deviceand/or within the cryoballoon 26. Additionally, a quadrapolar impedancemeasurement electrode configuration may be used to remove contact of theelectrode with tissue as a confusing factor.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings without departing from the scope andspirit of the invention.

1. A cryoablation device, comprising: an elongate body having a proximalportion and a distal portion opposite the proximal portion; anexpandable element coupled to the distal portion of the elongate body; afirst electrode disposed proximal to the expandable element; a shaftdisposed distal to the expandable element; a plurality of discreteelectrodes disposed circumferentially about the shaft, each of theplurality of discrete electrodes being spaced a distance apart; and atleast one thermocouple disposed distal to the first electrode.
 2. Thedevice of claim 1, wherein the first electrode is a reference electrode.3. The device of claim 1, wherein the expandable element is acryoballoon.
 4. The device of claim 1, wherein the plurality of discreteelectrodes are four discrete electrodes spaced an equal distance apartfrom one another.
 5. The device of claim 1, wherein the plurality ofdiscrete electrodes are disposed immediately distal to the expandableelement.
 6. The device of claim 5, wherein each of the plurality ofdiscrete electrodes abut the expandable element.
 7. The device of claim1, wherein the at least one thermocouple is disposed 2 mm distal to theplurality of discrete electrodes.
 8. The device of claim 1, furtherincluding a longitudinal axis, the plurality of discrete electrodesbeing radially arranged about the longitudinal axis.
 9. The device ofclaim 1, wherein the at least one thermocouple is disposed proximate tothe plurality of discrete electrodes.
 10. The device of claim 1, whereinthe first electrode is disposed circumferentially about the expandableelement.
 11. A system for cryoablating tissue, comprising: acryoablation device, including: an elongate body having a proximalportion and a distal portion opposite the proximal portion; a cryoballoncoupled to the distal portion of the elongate body; a first electrodedisposed proximal to the cryoballon; a shaft disposed distal to thecryoballon; a plurality of discrete electrodes disposedcircumferentially about the shaft, each of the plurality of discreteelectrodes being spaced a distance apart; and at least one thermocoupledisposed distal to the first electrode; a console including a processor,the processor configured to: receive impedance measurements recorded bythe first electrode and the plurality of discrete electrodes; receivetemperature measurements recorded by the at least one thermocouple;compare impedance measured by the first electrode and the plurality ofdiscrete electrodes; and determine if the cryoballoon is creating apermanent lesion, the determination being based upon at least one of theimpedance measurement of the first electrode, the impedance measurementof the plurality of discrete electrodes, and the temperature measurementby the at least one thermocouple.
 12. The system of claim 11, whereinthe first electrode is a reference electrode.
 13. The system of claim11, wherein the plurality of discrete electrodes are four discreteelectrodes spaced an equal distance apart from one another.
 14. Thesystem of claim 13, wherein the plurality of discrete electrodes aredisposed immediately distal to the cryoballoon.
 15. The system of claim14, wherein each of the plurality of discrete electrodes abut thecryoballoon.
 16. The system of claim 11, wherein the processor isfurther configured to compare impedance measured by the first electrodeto impedance measured by the plurality of discrete electrodes.
 17. Thesystem of claim 11, wherein the processor is further configured toindividually monitor each of the plurality of discrete electrodes andevaluate a symmetry of the impedance measurements from each of theplurality of discrete electrodes.
 18. The system of claim 11, whereinthe at least one thermocouple is disposed 2 mm distal to the pluralityof discrete electrodes.
 19. The system of claim 11, wherein the firstelectrode is disposed circumferentially about the cryoballoon.
 20. Asystem for cryoablating tissue, comprising: a cryoablation device,including: an elongate body having a proximal portion and a distalportion opposite the proximal portion; a cryoballoon coupled to thedistal portion of the elongate body; a reference electrode disposedproximal to the cryoballoon and disposed circumferentially about thecryoballoon; a shaft disposed distal to the cryoballoon; four discreteelectrodes disposed circumferentially about the shaft, each of the fourdiscrete electrodes being spaced an equal distance apart, and each ofthe four discrete electrodes abutting the cryoballoon; and at least onethermocouple disposed distal to the reference electrode and disposed 2mm distal to the four discrete electrodes; a console including aprocessor, the processor configured to: receive impedance measurementsrecorded by the reference electrode and the four discrete electrodes;receive temperature measurements recorded by the at least onethermocouple; compare impedance measured by the reference electrode andthe four discrete electrodes; and determine if the cryoballoon iscreating a permanent lesion, the determination being based upon at leastone of the impedance measurement of the reference electrode, theimpedance measurement of the four discrete electrodes, and thetemperature measurement by the at least one thermocouple.